PROJECT SUMMARY The prevalence of hypertension is greater in older (?65 years) women than in older men, while the blood pressure (BP) control rate is lower in older women in the United States. Uncontrolled hypertension is a major risk factor for cardiovascular morbidity and mortality. Despite standard therapy and adherence to optimal drug regimens, over 50% of older hypertensive women still have inadequate BP control (e.g. >140/90 mmHg), and the control rate is further reduced with more aggressive BP targets recommended recently by the new 2017 ACC/AHA Hypertension Guidelines. Thus, the effectiveness of drug treatment alone in the control of hypertension among older women is limited; hence, non-pharmacological approaches are also needed to help reduce BP and cardiovascular morbidity and mortality in older hypertensive women. One adjuvant, non- pharmacological approach that offers promise in lowering BP is ?heat therapy?. Indeed, repeated (chronic) whole-body heat exposure has been found to decrease BP in healthy humans. Whether this is also true after regional limb heating in hypertensive patients is unknown. The global objectives of this research project are to investigate the BP lowering effect of home-based lower leg heat therapy in older women with hypertension, and to examine the impact of this therapeutic modality on neural-vascular health in these patients. Specific Aim 1 will test the hypothesis that chronic lower leg heat therapy combined with an antihypertensive drug is superior to drug treatment alone in lowering BP in older hypertensive women. We will randomly assign older hypertensive women to either an intervention group or a control group. Patients in the intervention group will perform 8 weeks of home-based lower leg heat therapy via water immersion up to the knee in a circulated bath (water temperature 42C, 4 times per week, 45 min per session), whereas patients in the control group will immerse their legs in a thermoneutral water bath (33C) at the same frequency and duration. All patients will also receive a fixed dose of chlorthalidone (a diuretic, 25 mg orally once daily). We will compare ambulatory BP, the BP control rate, and patient adherence and acceptability to treatment between the groups. Specific Aim 2 will test the hypothesis that chronic lower leg heat therapy will improve nitric oxide bioavailability which can decrease sympathetic vasoconstriction and improve vascular function in older hypertensive women. We will use state-of-the-art techniques of microneurography, Doppler ultrasound, applanation tonometry, and cutaneous microdialysis to assess sympathetic neural control, indices of conduit and resistance vessel vasodilator function, and interstitial metabolites (i.e. nitrate and nitrite) indicative of basal nitric oxide bioavailability in all patients enrolled in Aim 1 before and after 8 weeks of heat therapy. Information obtained from this research project will guide evidence-based clinical practice. It is anticipated that our study may lead to revision of hypertension guidelines to incorporate home-based heat therapy as adjuvant to antihypertensive drug(s) for older women, as well as other patient populations.